Miniaturization of chemical analysis systems has been desirable in fabricating compact liquid chromatographs and capillary electrophoresis chips. The prior art in MEMS technology have been mainly in the field of UV absorbance and electro-chemi-luminescence for on-chip detection. These optical methods are not viable for most biomolecules, e.g. protein and peptide, detection. It is desirable to have an on-chip detection element that has the femtomole sensitivity and versatility provided by a mass spectrometer (MS). MS also allows minimal liquid sample preparation.
Most conventional mass spectrometers are too large to accommodate MEMS systems. Hence, a method and apparatus which couples MEMS systems to a non-MEMS mass spectrometer is desired. More specifically, an on-chip interface that has the advantage of directly connecting the two systems together is desired.
MEMS chemical systems can generate ions for MS analysis with electrospray ionization (ESI). ESI can detect large molecules, e.g. molecules up to 200 KDa, directly from the liquid sample. This capability is desirable for MEMS protein and peptide analysis. Bio-assaLy methods such as polymerase chain reaction (PCR) amplification are not as useful in such a large molecule range. Other advantages of ESI include: soft ionization, ease of use, and complete compatibility with liquid chromatography.
Conventional ESI is done using glass capillaries. If MEMS devices are interfaced using this conventional technique, the liquid sample needs to be piped out with capillary tubing to the MS intake. There, the sample molecules are ionized and then, detected. Dead volume is the internal volume that the liquid takes up from the inlet of the device to the actual point of analysis. The point of analysis in the case of ESI is where the droplets are sprayed out. Smaller dead volume is advantageous. Increase in overall system dead volume can obviate certain advantages gained in MEMS miniaturization of the liquid separation stage. The present disclosure teaches decreasing the overall system dead volume.
The present disclosure provides an apparatus that can couple MEMS systems and mass spectrometry systems using ESI without these drawbacks. Recently, in "Multichannel Microchip Electrospray Mass Spectrometry", Xue et al, Anal. Chem, 1997, vol. 69, p. 426-430 and in "Generating Electrospray from Microchip Devices Using Electrosmotic Pumping", Ramsey et al, Anal. Chem, 1997, vol. 69, p. 1174-1178; Xue et al and Ramsey et al have both tried interfacing flat-edged glass micro-channels with cross-sections of 10 .mu.m deep by 60 .mu.m wide to an MS and demonstrating electirospray (ES).
The present disclosure uses an overhanging silicon nitride micro-channel. The preferred dimensions are 1 .mu.m high by 2 .mu.m wide. This micro-channel dramatically reduces the wetted surface area at the ESI tip. Reduction of this orifice diameter and tip surface area correspondingly reduces the size of the fluid cone during electrospray, thus reducing the internal volume that the liquid occupies from the inlet of the device to the actual point of analysis. This internal volume is called the dead volume. In addition to reducing dead volume, the nozzle has integrated particle filter structures. These filter structures functions to reduce MEMS ESI tip clogging.